Centromeres license the mitotic condensation of yeast chromosome arms

During mitosis, chromatin condensation shapes chromosomes as separate, rigid and compacted sister-chromatids to facilitate their segregation. Here, we show that unlike wild type yeast chromosomes, non-chromosomal DNA circles and chromosomes lacking a centromere fail to condense during mitosis. Genetics and ChIP-seq experiments establish that the centromere functions in chromosome condensation upstream of the kinases Aurora B and Bub1. Downstream of Aurora B and Bub1, Shugoshin and the deacetylase Hst2 facilitated spreading of the condensation signal from the pericentromeric region to the chromosome arms. Targeting Aurora B to DNA circles or centromere-ablated chromosomes, or releasing Shugoshin from PP2A-dependent inhibition bypassed the centromere requirement for condensation and enhanced the mitotic stability of DNA circles. Our data indicate that yeast cells license in a centromere-dependent manner the chromosome-autonomous condensation of their chromatin, excluding non-centromeric DNA from this process and thereby inhibiting their propagation.在有丝分裂过程中，染色质凝聚（chromatin condensation）会将染色体塑造为彼此分离、结构刚性且紧密压缩的姐妹染色单体（sister chromatids），以利于染色体的分离。本研究发现，与野生型酵母染色体不同，非染色体DNA环（non-chromosomal DNA circles）以及缺乏着丝粒（centromere）的染色体无法在有丝分裂过程中发生凝聚。遗传学实验与染色质免疫共沉淀测序（ChIP-seq）结果证实，着丝粒在染色体凝聚过程中发挥调控功能，且其作用位点位于激酶Aurora B与Bub1的上游。在Aurora B与Bub1的下游通路中，Shugoshin与去乙酰化酶Hst2可促进凝聚信号从着丝粒旁区（pericentromeric region）向染色体臂扩散。将Aurora B靶向定位至DNA环或着丝粒缺失的染色体，或是解除Shugoshin所受的蛋白磷酸酶2A（Protein Phosphatase 2A）依赖性抑制，均可绕过着丝粒对染色体凝聚的调控需求，并提升DNA环的有丝分裂稳定性。本研究数据表明，酵母细胞以着丝粒依赖性方式赋予染色质以染色体自主性凝聚的能力，将非着丝粒DNA排除在此过程之外，从而抑制这类DNA的增殖传播。